Difluoroxalatostannate(ii) complexes

ABSTRACT

A new genus of compositions of matter, namely, difluoroxalatostannate(II) complexes has been discovered. These compounds when incorporated into oral compositions for dental caries prophylaxis (e.g., as a constituent of a dentifrice, prophylaxis paste, or mouthwash), have demonstrated substantial utility as an anticariogenic agent.

United States Patent Katz 1 July 18, 1972 [54] DIFLUOROXALATOSTANNATEHI)COMPLEXES Primary Examiner-Richard L. Huff Attorney-Ronald L. Engel,Daniel W. Vittum, Jr., Gomer W. [72] Inventor: Simon Katz, Indianapolis,Ind. Walters, John watem and James Amend 73 Assi nee: Indiana UniversitFoundation Bloomin l l g ton, Ind. y g [57 ABSTRACT A new genus ofcompositions of matter, namely, difluorox- [22] Filed Jan. 1971alatostannatefll) complexes has been discovered. These com- [21] Appl.No.: 108,227 ounds when incorporated into oral compositions for dentalcaries prophylaxis (e.g., as a constituent of a dentifrice, prophylaxispaste, or mouthwash), have demonstrated sub- 52 U.S. c| ..424/s2,260/429.7 stamial utility as an amicariogenic agent [51] lnt.Cl...A61k7/16 58] Field of Search ..424/52; 260/429] 19 Claims, No Drawings1 DIFLUOROXALA'IOSTANNATE(II) COMPLEXES BACKGROUND OF THE INVENTION 1.Field of the Invention This invention relates to a new genus ofcompounds, difluoroxalatostannate (II) complexes and to the use thereofas anticariogenic agents in oral compositions for caries prophylaxis. Bythe term oral composition -is meant a product which in the ordinarycourse of usage is not intentionally ingested, but rather is retained inthe oral cavity so as to contact the oral hard tissues.

2. Description of the Prior Art It is commonly recognized that thepresence of microquantities of fluoride in drinking water (e.g., 1.0micrograms fluoride per milliliter) has a pronounced effect on reducingthe incidence of dental caries in permanent teeth of children consumingsuch water from birth through 8 years of age. Fluoride salts have beenintroduced into public water supplies in many communities with goodresults. This method of caries prophylaxis is not available, however, toa large number of people whose drinking water is obtained from small,private fluoride-deficient sources such as individual wells, etc.Further, the addition of fluoride to common public water sources is notalways accepted or permitted.

Topical applications of aqueous fluoride solutions by dentists or dentalhygienists provide an excellent measure of protection against dentalcaries. Various fluoride compounds have been employed for this purpose,including sodium fluoride and stannous fluoride. Likewise, dentifricesand mouthwash compositions comprising various fluoride compounds areknown to exhibit anticariogenic effectiveness.

Although effective dental caries protection has been obtained throughthe use of the aforementioned fluoride compounds, certain physicallimitations have limited the efficacy of these agents. For example, theutility of certain prior art anticariogenic agents has been limited bythe extent of their solubility in an aqueous media. For example, sodiumfluoride (NaF) is only soluble to the extent of about 4 percent inwater. Solubility can, of course, limit the quantity of anticariogenicions provided by an agent that is available for reaction with the toothsurface. The relative insolubility of certain of the prior artanticariogenic agents limits the value of the same for the use inprophylactic paste compositions since the volume of water inprophylactic paste is substantially limited.

Finally, certain of the known prior art anticariogenic agents have beenrelatively unstable in aqueous solutions. For example, stannous ions aresubject to oxidation and hydrolysis and, for that reason stannouscontaining compositions must ordinarily be in freshly prepared form ormust be used in conjunction with complexing anions in order to obtainits optimal anticariogenic effect.

For these reasons and others, dental researchers have continued theirefforts to develop new compositions which are not onlyanticariogenically more effective, but which also exhibit none of thedifficulties associated with certain of the prior art anticariogenicagents.

It is generally believed that fluoride ion in functioning as a topicalanticariogenic agent acts through the formation of insoluble calciumfluoride on the surface of the toothenamel. It has also been suggestedthat the incorporation of fluoride into the enamel lattice through thesubstitution of fluoride for hydroxyl groups in the hydroxyapatitecrystal of the enamel (so as to form fluoride-substitutedhydroxyapatite) decreases the solubility of the enamel in oral acids.

The degree of the reaction between the fluoride and the enamel islimited by the relatively close proximity of the enamel crystals and bythe formation of the calcium fluoride precipitate itself. In fact, theproximity between enamel crystals (which serves to prevent the passageof fluoride ions into the crystal lattice) has been suggested to be themain factor limiting the deep penetration of topical fluoride into theenamel crystal lattice. In addition to the electrostatic and mechanicalbarriers proposed by the close proximity of the enamel crystal, a secondfactor apparently limiting the possibility of fluoride uptake is theenergy required for the fluorideenamel reaction to proceed.

Because of the limitations posed on fluoride uptake, it would bedesirable to provide a means for increasing the fluoride uptake andpenetration into the enamel lattice, and this invention therefore hasfor its principal object to provide a new genus of compounds,difluoroxalatostannate (II) complexes, which increase the uptake of thefluoride ion by and reduce the acid solubility of dental enamel.

It is a further related object of the present invention to provide a newgenus of compounds, difluoroxalatostannate (II) complexes, which exhibita high level of anticariogenic effectiveness and which are nontoxic toliving organisms at operable concentration levels.

A further object is to provide an adjunct to a topical fluoride systemcapable of temporarily loosening the enamel crystal lattice so as topermit fluoride ions to penetrate deeper, serving also to reduce thelattice energy so as to decrease the amount of energy required for afluoride-enamel reaction to proceed.

Yet another object of the present invention is to provide ananticariogenic agent of the character describedwhich is stable inaqueous solutions even at relatively high concentration.

Another object is to provide new and unique oral compositionscharacterized by the inclusion of a chelating agent in combination witha source of soluble fluoride ion or of a chelating agent complexed to afluoride moiety.

A related object involves the provision of oral compositions comprisinga source of soluble fluoride ion and a chelating agent to enhance theuptake of fluoride ion by the reduction of enamel solubility of dentalenamel.

Yet another object is to provide new and improved methods for topicallyreducing the incidence of dental caries.

Another object is to provide a new method of increasing the uptake oftin (II) ions into the dental enamel crystal lattice.

SUMMARY OF THE INVENTION DETAILED DESCRIPTION OF THE PREFERREDEMBODIMENTS In accordance with the present invention, there have beendiscovered new compositions of matter, namely difluoroxalatostannate(ll)complexes of the formula M [SnF (C O,)]

where M+ is a metal or ion such as potassium, sodium or ammonium. Inaddition, water of hydration may be present in the molecule. Thedifluoroxalatostannatefll) complexes of this invention have, as willhereinafter be described in detail, demonstrated effectiveness asanticariogenic agents useful in oral compositions.

PREPARATION AND PROPERTIES Difluoroxalatostannate(ll) complexes may beprepared by various methods. In order to utilize the chelating abilityof oxalic acid, H C O plus the known cariostatic effect of tin(II) ions,the use of stannous oxalate was thought to be advantageous. Stannousoxalate, SnC O is, however, insoluble in water. However, upon addition.of sodium fluoride, NaF, it was discovered that the stannous oxalateprecipitate became soluble. Complete solubility and completetransparency of the solution was found to occur when the fluoride saltwas added to the oxalate salt in a 2:1 molar ratio. The pH of theresulting solution is 4.8. It was found that stannous oxalate reactssimilarly with potassium fluoride KFQH O, to provide a soluble productwhere the fluoride to oxalate ratio was 2:1.

Another method of preparing the difluoroxalatostannate(ll) complexes ofthis invention involves the utilization of alkali metal hydroxides andhydrofluoric acid. A 1 mole stannous oxalate suspension having a pH ofabout 3.0 is prepared. Upon the addition of 2 moles of hydrofluoricacid, HF, the pH is reduced to 1.7-1.8 but the suspension remains turbidunder stirring. Upon the addition of diluted sodium hydroxide, NaOH, thesolution becomes clear when the pH approaches 4.8.

Another method of preparing the difluoroxalatostannatefll) complexes ofthis invention involves the use of the alkali metal oxalate and stannousfluoride. One mole of the metal oxalate (sodium or potassium oxalate) isslowly added to a solution containing one mole of stannous fluoride. ThepH of the solution at that point will be found to be 4.8.

The products of the reactions described above, were separated from theirrespective solutions through evaporation to almost dryness followed byprecipitation by alcohol and dessication under a vacuum over silca gel.The resulting products were white crystalline solids. They are extremelysoluble in water, but insoluble in alcohol. Solutions of these compoundsare clear at pHs up to approximately 5.5. Above pH 5.5 a whitening ofthe solution occurs, and a white precipitate can be observed. Somewhitening also occurs at pH 5.0 as a function ofsolution aging.

Further, it was noted that the sodium complex, sodiumdifluoroxalatostannate(ll), Na [SnF (C O has a melting point between 280and 285 C., and the potassium complex, potassiumdifluoroxalatostannate(ll), K [SnF (C O has a melting point between 230and 240 C.

Sodium difluoroxalatostannatefll) may be conveniently prepared by mixing10.0 g of stannous oxalate into 100 ml of redistilled water. 4.06 g ofsodium fluoride are mixed into the solution. The product of thisreaction may be separated by evaporation as discussed above. Similarly,potassium difluoroxalatostannate(ll) may be conveniently prepared bymixing g of stannous oxalate into 100 ml of redistilled water and mixinginto that solution 5.6 g of potassium fluoride. 9.2 g of potassiumfluoride dihydrate (KF-ZH O) can be substituted for the 5.6 g ofpotassium fluoride in this latter reaction. The products of thesereactions may be separated by evaporation as discussed above. Followinga similar procedure, the ammonium difluoroxalatostannate(ll) may beconveniently prepared by dissolving 4.13 g stannous fluoride in 200 mldistilled water. While stirring this mixture, 3.72 g ammonium oxalatemonohydrate is added. The products of this reaction may be separated byevaporation as discussed above.

It was further observed, by X-ray diffraction, that the product of thereaction of sodium oxalate and stannous fluon'de was identical to thatformed by stannous oxalate and sodium fluoride. Similarly, the productof potassium oxalate and stannous fluoride was identical to thatobtained with stannous oxalate and potassium fluoride. Both potassiumdifluoroxalatostannate(ll) and sodium difluoroxalatostannate(ll) havebeen characterized according to the conventional Hull-Debye-ScherrerX-ray diffraction powder technique in order to produce a film record.Exposures were made using standard X-ray diffraction camera (diameter114.7 mm). As is well known to one skilled in the art, the techniquecauses crystalline materials to diffract X-rays according to a patternspecific for each compound. The X-rays expose a film according to aspecific pattern, which appears on the film as characteristic lines, theinterplanar spacing and the relative intensity of which may be measuredin order to identify the compound. The pattern for potassium stannousfluoroxalate and sodium stannous fluoroxalate are distinctive anddistinguish these compounds from other compounds, particularly thestarting materials from which they are made.

ORAL COMPOSITIONS COMPRISING DIFLUOROXALATOSTANNATE(ll) COMPLEXES Thedifluoroxalatonstannate(ll) complexes of this invention havedemonstrated utility as anticariogenic agents for use in oralcompositions which comprise carriers such as abrasives,

water, and other nontoxic materials, in addition to the' tions producedin accordance with the present invention com prise from about 0.1 toabout 10 percent by weight of one or more difluoroxalatostannates.

Oral compositions designed for relatively frequent use, such asdentifrices and mouthwashes, will contain lower levels ofdifluoroxalatostannate(ll) complexes than compositions which are appliedless frequently (e.g., prophylactic pastes and topical solutions). Thus,dentifrices preferably contain from about 0.1 percent up to about 1.5percent by weight of difluoroxalatostannate(ll) complexes, whereasprophylaxis pastes preferably comprise about 2 to 10 percent metaldifluoroxalatostannate(ll) complexes by weight and aqueous topicalsolutions preferably comprise about 1.0 to 8.0 percentdifluoroxalatostannatefll) complexes.

The cleaning and polishing material in dentifrices of this inventionshould be ionically compatible with tin(ll) and fluoride ions and cancomprise from about 20 to percent by weight of the total composition.Preferably, toothpastes contain from 20 to 60 percent cleaning andpolishing agent by weight, and tooth powders contain from 60 to 95percent by weight. Examples of suitable cleaning and polishing agentssuitable for use in a dentifrice include, without limitation, calciumpyrophosphate, Ca P O,; calcium hydrogen phosphate dihydrate, CaHPO'2l-l O; insoluble sodium metaphosphate, (NaPO calcium carbonate, CaCOmelamine formaldehyde resins (U.S. Pat. No. 3,070,510); and preferablyzirconium silicate and mixtures of zirconium silicate with othercleaning and polishing agents as disclosed in US. Pat. No. 3,450,813.Mixtures of these cleaning and polishing agents may also be used.

Toothpastes require a binder substance to impart desired textureproperties. Natural gum binders such as gum tragacanth, gum karaya, gumarabic, etc., and seaweed derivatives such as lrish moss, and alginates,and water soluble cellulose derivatives such as hydroxyethyl celluloseand sodiumcarboxymethyl cellulose, can be used for this purpose.Desirably those materials are employed which are most compatible withthe fluoride ion. Binders which have no ionic groups, such ashydroxyethyl cellulose, are especially preferred. Improvements intexture can also be attained by including an additional material such ascolloidal magnesium aluminum silicate.

Thickening agents in an amount of from 0.5 to 5.0 percent by weight canbe used to form a satisfactory toothpaste.

Toothpaste conventionally contains sudsing agents. Suitable sudsingagents include, but are not limited to, water-soluble alkyl sulfateshaving from eight to 18 carbon atoms in the alkyl radical, such assodium lauryl sulfate, water-soluble salts of sulfonated monoglycerides,fatty acids having from 10 to 18 carbon atoms in the alkyl radical suchas sodium coconut monoglyceride sulfonate, salts of the fatty acidamides of taurines such as sodium-N-methyl palmitoyl tauride, and saltsof fatty esters of isethionic acid.

Sudsing agents can be used in the compositions of this invention in theamount from about 0.5 percent to about 5.0 percent by weight of thetotal composition.

It is also desirable to include some humectant material in toothpaste tokeep it from hardening. Materials commonly used for this purpose includeglycerine, sorbitol and other polyhydric alcohols. Humectants cancomprise up to 35 percent of the toothpaste composition.

Flavoring materials may be included in the toothpaste formulation,including small amounts of oils of Wintergreen and peppermint, andsweetening agents such as saccharine, dextrose and levulose.

Exemplary dentifrice formulations are given in the following examples.

EXAMPLE I Constituent Percent by Weight Potassiumdifluoroxalatostannatefll) *An ammonium salt of a condensation productof NH and Pp commercially available from the Victor Chemical Companyunder the trademark Vitamide". e.g.,

n u O H4NOPOPONH4 H H I H4NOfi-O H ONH4 0 o H EXAMPLE I1 ConstituentPercent by Weight Potassium difluoroxalatostannate(ll) 0.87 Distilledwater 20.00 Sorbitol 13.00 Buffer (KH Phtalate) 1.20 Fumaric Acid 0.20Ammonium hydroxide (to adjust pH) 0.33 (approx.) Veegum 0.40 Sodiumlaryl sulfate 1.80 Acid washed talc 30.00 Zirconium silicate 12.00Glycerin 15.00 Binder (CMC) 4.50 Flavoring agents 0.68 100.00

EXAMPLE Ill Constituent Percent by Weight Sodiumdifluoroxalatostannate(ll) 0.74 Distilled water 18.00 Sorbitol 13.60Buffer (KH Phtalate) 1.20 Hydroxyethylenediaminotetraacetic acid 0.10Ammonium hydroxide (to adjust pH) 0.75 (approx.) Vee um 0.40 Sodiumalkyl aryl sulfonate 2.00 Resin abrasive 42.00 Glycerin 15.50Carboxymethylcellulose 5.00 Flavoring agents 0.70 100.00

*U. S. Patent No. 3,070,510

EXAMPLE 1V Constituent Percent by Weight Ammoniumdifluoroxalatostannate(ll) 0.72 Distilled water 18.00 Glycerin 15.00Sorbitol 15.00 Buffer (KH Phtalate) 1.20 Fumaric acid 0.20

Potassium hydroxide (to adjust pH) Veegum Sodium alkyl sulfate 0.78(approx.) 0.40 2.00

Dicalcium phosphate dihydratc 33.55 Dicalcium phosphate, anhydrous 7.45CMC (binder) 5.00 Flavoring agents 0.70

EXAMPLE V Constituent Percent by Weight Sodiumdifluoroxalatostannate(ll) 0.75 Distilled water 22.00 Sorbitol 12.00Methyliminodiacetic acid 0.10 Buffer (KH Phtalate) 1.20 lmidazole (toadjust pH) 0.85 (approx.) Sodium lauryl sulfate 2.00 Calciumpyrophosphate 42.00 Veegum 0.40 Glycerin 14.00 CMC 4.00 Flavoring agents0.70

An exemplary formulation of a nonabrasive dentifrice is given in thefollowing examples.

EXAMPLE Vl-(Non-Abrasive Dentifrice) Constituent Percent by WeightPotassium difluoroxalatostannate(ll) 0.87 Distilled water 40.00 Sorbitol30.00 Fumaric acid 00.15 Buffer (KH Phtalate) 1.00 lmidazole (to adjustpH) 0.26 (approx.) Sodium alkyl sulfonate 2.00 Glycerin 19.00 Keltrol6.00 Flavoring agents 0.70 100.00

EXAMPLE Vl1(Non-Abrasive Dentifrice) Constituent Percent by WeightSodium difluoroxalatostannate(ll) 0.75 Distilled water 35.00 Sorbitol35.00 Victamide 3.46 Fumaric acid 0.20 Ammonium hydroxide (to adjust pH)0.59 (approx.) Sodium lauryl sulfate 2.00 Glycerin 17.50 CMC 5.00Flavoring agents 0.50 100.00

EXAMPLE VIII-(Prophylactic paste) treatment. Each mandibular hemijaw isremoved, the clinical C Sn t P b w ht crowns of each are decalcified in0.2N(pH sodium acetate y buffer for 20 minutes, and the decalcificationsolutions are analyzed for phosphorus by a colorimetric method (Fisk andP0tas v 'l aws a awfl 8- 5 Subbarow, The Colorimetric Determination ofPhosphorus, s 'g Journal of Biological Chemistry, 66:375, 1925).Phosphorus Glycerin liberation of the teeth topically treated with thevarious alkali Sorbitol 2.50 metal stannous fluoroxalate containingsolutions was comz 88 pared to that of teeth similarly treated withdistilled water coni g dioxide trol solutions, and the result of suchcomparison is reported as Sodium trimetaphosphate ,00 a percentagereduction of enamel solubility (i.e., rat ESR). Flavoring agents 0.95Table -2 presents the results of tests conducted using solutions 100-00of sodium and potassium difluoroxalatostannatefll) having a fluoridecontent of 1,000 m. The data show an ESR value of PP P E [X (pmphy]acticpaste) over 74 percent for the fluoroxalatostannate complexes, ascompared to control animals to which distilled water was apconsllmemPercel" y Weigh! plied. By way of comparison, the ESR effectiveness of astannous fluoride solution containing 1,000 ppmF in the same test Sodiumdifluoroxalatostannatefll) 10.60 P Zirconium silicate 49.00 TABLE 2Stannous oxide 5.00 w r 20m The Efiect of Different Fluoride Compoundsin Aoueous Solution Upon the Rate of Acid Dissolution of Rat EnamelGlycerin 2.50 Sorbitol 2.00 Procedure: Veegum 1. 5 rats were used pergroup. CMC 1.20 2. The animals were given three, thirty-second topicalapplications Sodium trimetaphosphate 8.00 with the freshly preparedsolutions. The pH was adiusted as needed Flavoring agents 1.00 with NNaOH' 100 00 3. One hour after the final topical the animals weresacrificed, the hemijaws removed and the rate of dissolution of enameldetermined as a function of the amount of phosphorus removed from thehemiiaws by 20-minute immersion in a .1 N, pH 4.0 acetate buffer.ANTICARIOGENIC EFFECT lVENESS FSR The anticariogenic effectiveness ofalkali metal stannous $3; Mean gP g: fluoroxalate complexes may bedemonstrated by the in vitro Solution tested nI l r as c t) test? whichwhole human teeth or in f caries Controldistilled water... Net. 1o '84.75:l:4.1 penence in rats (standard experimental animals for an-$tem1011$g})lwride 10 47-22i3-3 44-28 ticariogenic studies). The effectof various compositions in gggfi- 5.0 m 355g 74,81 reducing the rate ofdissolution of dental enamel in acid is also gf a reliable indicator ofanticariogenticy. The effect of different -53m (jifiumm 10 19 035 1};77v 55 dental compositions on the rate of acid dissolution of enamellatostannflte ma b d db be r ilk y e etermlne y a num r 0 tests we nownin the art. 40 The particular test described herein comprises acomparison 'fie 8110f Ofthe meanof acid dissolution of a given toothafter an in vitro treatment Si ilar te t e erformed using a dentifricein vivo as with a given test composition. The comparison is expressed asfollows. The teeth of a group of suitably selected test rats are ESR,that is, enamel solubility reduction and the procedure given 30-secondapplications at 30-minute intervals of a employed is well accepted andhas been described in detail dentifrice with an active anticariogenicsystem composed of previ ly (Blmnef and e 361897, potassiumdilluoroxalatostannatefll) complexes, (F=l000 The results of testsutilizing solutions comprising potassium ppm), 0.15 percent fumaric acidand 2.5 percent victamide. difluoroxalatostannatefll) having a fluorideion content of at The dentifrice has a pH of approximately 4.6. Theanimals are least 1,000 ppm and a pH of 5.0 are presented in Table l.sacrificed 1 hour after the last brushing, and the ESR deter- These dataillustrate an ESR of approximately 95.4 percent or mined in accordancewith the above procedure. The results of more. These data illustratethat the difluoroxalatostannatefll) this test are presented in Table 3.These data illustrate an ESR complexes demonstrate substantialanticariogenic efficacy, value of percent or better as compared tocontrol animals. and further, substantial anticariogenic efficacy overand above These data also illustrate that a commercially availablestannous fluoride, SnF which in the same test provides ESR fluoridecontaining dentifrice resulted in an ESR of 29 percent results rangingfrom to percent. 55 as compared to the control animals. Therefore, thesedata i1- lustrate that a stannous difluoroxalatostannatefll) complexTABLE 1 containing dentifrice has substantial anticariogenic efficacy Invitro ESR on whole human enamel using four methods of preparing andSubstantial car ogen c efficacy 0V6! commercially the iiuol roxalatecomplex at a concentration such as to provide 1,000 il bl fl idcontaining d if i I21 n P 0 TABLE 3 Mg phosphorus released The effect ofdifierent dentifrice formulations upon the rate of enamel Percentdissolution in the rat Before After ESR =1; Fluoroxalate systemtreattreatstandard Procedure; prepared wltli pH ment meat error 1. 5animals were used per group.

5 2. The animals were given three thirty-second brushings. 1. Sn oxalateplus KF.2H,O 5. 0 16.99 28 98. 15:1. 9 3. One hour after the finalbrushing the animals were sacr ficed, the 2. oxalic-acid plus SnF, KOH.5. 0 23. 68 18 98. 8=l=1. 5 hemijawsremoved and the rate of dissolutionof enamel determined 3-- Sn oxalate plus HF KOH 5. O 20. 80 .74 96.3:111. O as a function of the amount of phosphorus removed from thehemi- 4 K1 Oxalate plus S11F3 5.0 24. 14 .84 97. 8:1:22 laws by a20-minute immersion period in a .1 N, ph 4.0 acetate 5. (NH4); oxalateplus SnFz. 5. 0 23.50 1. 11 95. 4i1. 8 buffer solution.

The pH was ad usted to 5.0 with diluted OH. 70 No.

Brushhemi- Mean g Percent Dentil'rice l g, pH laws phosphorus ESR Rattooth ESR maybe determined in vivo as follows. The Control active 10 72i515 teeth of a group of suitably selected test rats are given three wmum py p p e 4.1 10 62.69=1:3.8 28.98 30-second topical applications at30-minute intervals with 9 solutions containing various alkali metalstannous fluoroxalate 75 (II) (F= i p- 4.6 10 26.17;i=l.8 70. 35

complexes. The animals are sacrificed 1 hour after the last Standarderror of the mean.

ANIMAL TOXICITY In addition to exhibiting a high level of anticariogeniceffectiveness, the difluoroxalatostannatefll) complexes of the presentinvention may be safely utilized in animal organisms without anydangerous side effects. The toxicity of difluoroxalatostannate(ll) saltscompare quite favorably with the other anticariogenic fluorides as shownby the following experimental studies. The acute toxicity of thedifluoroxalatostannate( ll) complexes has been determined in mice(standard experimental animals for this purpose), and these data aregiven in Table 4. The toxicity is expressed in terms of an LD which isthe lethal does for 50 percent of the animals treated (within 24 hours).

TABLE 4 Comparative Acute Toxicity Data in Mice LD Dosage Fluoride Routeof mg/F/kg Mg Cpdlkg Compound I Administration Body Weight Body WeightNaF Oral 36 80 SnF Oral 35-36 l45l50 K,[SnF (C 04)] Oral 52 443Na,[SnF,(C O.)] Oral 61 468 Based on the data of Table 4 it would appearthat the acute LD of potassium difluoroxalatostannatefll) is about 52 mgF/kg body weight and the LD of sodium difluoroxalatostannate(ll) isabout 61 mg F/kg body weight. In comparison, the acute LD value forsodium fluoride is 36 mg F/kg body weight.

Thus, the difluoroxalatostannatefll) salts of this invention represent asubstantial advance in the dental arts and provide safe and effectiveadjuvants for use in oral compositions for dental caries prophylaxis.

lclaim:

1. Oral compositions for dental caries prophylaxis comprisprophylaxiscomprising:

about 0.1 to 10.0 percent by weight of at least onedifluoroxalatostannate of the formula M [SnF- (C O where M is potassium.

4. Oral compositions, as claimed in claim 1, for dental cariesprophylaxis comprising:

about 0.l to 10.0 percent by weight of at least onedifluoroxalatostannate of the formula M [SnF,(C O,,)] where M isammonium.

5. An oral composition, as claimed in claim I, wherein the compositionis a dentifrice and wherein the difluoroxalatostannate is present at alevel from about 0.1 to L5 percent by weight.

6. An oral composition, as claimed in claim 5, further comprising about20 to 60 percent of at least one compatible cleaning and polishingagent.

7. An oral composition, as claimed in claim 6, where M is sodium.

8. An oral composition, as claimed in claim 6, where M is potassium.

9. An oral composition, as claimed in claim 6, where M is ammonium.

10. An oral composition, as claimed in claim 1, wherein the compositionis prophylactic paste and wherein the difluoroxalatostannate is presentat a level from about 2 to 10 percent by weight.

11. An oral composition, as claimed in claim 10, further comprisingabout 20 to percent of a compatible cleaning and polishing agent.

12. An oral composition, as claimed in claim 10, where M is sodium.

13. An oral composition, as claimed in claim 10, where M is potassium.

14. An oral composition, as claimed in claim 10, where M is ammonium.

15. An oral composition, as claimed in claim 1, wherein the compositionis an aqueous solution adapted for direct topical application to theteeth comprising about l to 8 percent by weight difluoroxalatostannate.

1 6. An oral composition, as claimed in claim 15, where M is sodium.

17. An oral composition, as claimed in claim 15, where M is potassium.

18. An oral composition, as claimed in claim 15, where M is ammonium.

19. A method for increasing the dental caries resistance of teethcomprising the application thereto of an oral composition for cariesprophylaxis comprising about 0.1 to 10.0 percent by weight of at leastone metal difluoroxalatostannate of the formula M [SnF (C O,)], where Mis a member selected from the group consisting of sodium, potassium, andammoniurn.

2. Oral compositions, as claimed in claim 1, for dental cariesprophylaxis comprising: about 0.1 to 10.0 percent by weight of at leastone difluoroxalatostannate of the formula M2(SnF2(C2O4)) where M issodium.
 3. Oral compositions, as claimed in claim 1, for dental cariesprophylaxis comprising: about 0.1 to 10.0 percent by weight of at leastone difluoroxalatostannate of the formula M2(SnF2(C2O4)) where M ispotassium.
 4. Oral compositions, as claimed in claim 1, for dentalcaries prophylaxis comprising: about 0.1 to 10.0 percent by weight of atleast one difluoroxalatostannate of the formula M2(SnF2(C2O4)) where Mis ammonium.
 5. An oral composition, as claimed in claim 1, wherein thecomposition is a dentifrice and wherein the difluoroxalatostannate ispresent at a level from about 0.1 to 1.5 percent by weight.
 6. An oralcomposition, as claimed in claim 5, further comprising about 20 to 60percent of at least one compatible cleaning and polishing agent.
 7. Anoral composition, as claimed in claim 6, where M is sodium.
 8. An oralcomposition, as claimed in claim 6, where M is potassium.
 9. An oralcomposition, as claimed in claim 6, where M is ammonium.
 10. An oralcomposition, as claimed in claim 1, wherein the composition isprophylactic paste and wherein the difluoroxalatostannate is present ata level from about 2 to 10 percent by weight.
 11. An oral composition,as claimed in claim 10, further comprising about 20 to 95 percent of acompatible cleaning and polishing agent.
 12. An oral composition, asclaimed in claim 10, where M is sodium.
 13. An oral composition, asclaimed in claim 10, where M is potassium.
 14. An oral composition, asclaimed in claim 10, where M is ammonium.
 15. An oral composition, asclaimed in claim 1, wherein the composition is an aqueous solutionadapted for direct topical application to the teeth comprising about 1to 8 percent by weight difluoroxalatostannate.
 16. An oral composition,as claimed in claim 15, where M is sodium.
 17. An oral composition, asclaimed in claim 15, where M is potassium.
 18. An oral composition, asclaimed in claim 15, where M is ammonium.
 19. A method for increasingthe dental caries resistance of teeth comprising the application theretoof an oral composition for caries prophylaxis comprising about 0.1 to10.0 percent by weight of at least one metal difluoroxalatostannate ofthe formula M2(SnF2(C2O4)), where M is a member selected from the groupconsisting of sodium, potassium, and ammonium.